Of two patient populations totaling 82 patients, one in the United States and the other in Japan, we studied the cellular immune responses against S-antigen and interphotoreceptor retinoid binding protein as well as to fragments of each antigen. Behçet's disease, birdshot retinochoroidopathy, pars planitis, ocular sarcoid, sympathetic ophthalmia, and the Vogt-Koyanagi-Harada syndrome were diagnosed in these patients. The response profile of both antigens paralleled each other. This profile was more commonly seen in patients suffering from diseases affecting the retina. Responders reacting to both antigens or to several fragments of an antigen were present. This pattern of response was seen in 26 of the patients tested. Patients with uveitis appeared able to recognize several autoantigens. This might be a consequence of the breakdown of the blood-retinal barrier and may help perpetuate the inflammatory process. Several patients were capable of responding to more than one epitope of the same antigen, which indicates that there are major differences between the experimental model and human autoimmune diseases in the response to autoantigens. Both of these findings may to help develop new immunotherapeutic strategies in the treatment of uveitis.